Principal Investigator: Kuan Hong Wang
Kuan Hong Wang
Unit on Neural Circuits and Adaptive Behaviors
Clinical Brain Disorders Branch
Dr. Wang is chief of the Unit on Neural Circuits and Adaptive Behaviors in the Genes Cognition and Psychosis program at the National Institute of Mental Health. Dr. Wang received his B.A. in Biochemical Sciences from Harvard College and his Ph.D. from the University of California at San Francisco, where he studied the molecular regulators of sensory axon growth and branching during development with Marc Tessier-Lavigne. Dr. Wang obtained postdoctoral training with Susumu Tonegawa at the Massachusetts Institute of Technology, where he examined the ways in which cortical neurons respond to an animal's experience by directly visualizing the molecular activity of a given set of neurons over several days in the live animal. With this approach, he revealed a physiological function of neural activity regulated gene Arc in sharpening stimulus-specific responses in visual cortex.
Many psychiatric disorders are considered to have neurodevelopmental origins and are influenced by genetic and environmental risk factors. The long-term goal of Dr. Wang’s laboratory is to understand how genetic and experiential factors impact the developmental trajectory and functional architecture of brain circuits critically involved in psychiatric disorders in order to develop improved treatment and management for these diseases. Among the core deficits associated with serious psychiatric disability, the impairment of executive function, affecting the planning, initiation and regulation of goal-directed behaviors, has been increasingly highlighted as of central importance. Normal executive function in goal-directed behavior depends on the frontal lobe, and functional brain imaging studies have revealed altered activities in this brain region in patients suffering from schizophrenia, depression and drug addiction. However, much less is known about the cellular and molecular mechanisms by which genetic and environmental factors perturb the development and function of frontal cortical circuits. Lack of such knowledge has hampered the identification of key cellular targets and molecular pathways for therapeutic interventions. The current focus of Dr. Wang’s laboratory is to elucidate the basic cellular and molecular mechanisms underlying experience-dependent regulation of frontal cortical circuits in model organisms. A variety of cutting-edge technologies in molecular genetic engineering, in vivo multi-photon imaging, optogenetic neural modulation, electrophysiology, and behavioral analyses are being developed and integrated in the laboratory to perturb frontal cortical circuit development and function, and to investigate the ability of the circuit to change in response to both normal and pathological experience. Particularly, Dr. Wang’s group is interested in identifying and characterizing the molecular and cellular changes in the frontal cortical circuits that are regulated by the internal drives, environmental exposures and social interactions of an animal. Furthermore, Dr. Wang’s group is interested in examining the neurophysiological correlates of these molecular and cellular changes and determining the mechanisms by which these changes are integrated in the cortical circuits to control behavioral decisions and motor plans. Finally, Dr. Wang’s group is interested in evaluating the impacts of psychiatric risk factors and treatment strategies on experience-dependent molecular and cellular changes in the frontal cortical circuits through molecular genetic manipulation and optical imaging and probing.
In vivo two-photon imaging of experience-dependent molecular changes in cortical neurons. Cao VY, Ye Y, Mastwal SS, Lovinger DM, Costa RM, Wang KH. J Vis Exp. 2013 Jan 5;(71). pii: 50148. doi: 10.3791/50148. PMID: 23329071.
Optogenetic inactivation modifies monkey visuomotor behavior. Cavanaugh J, Monosov IE, McAlonan K, Berman R, Smith MK, Cao V, Wang KH, Boyden ES, Wurtz RH. Neuron. 2012 Dec 6;76(5):901-7. doi: 10.1016/j.neuron.2012.10.016. PMID: 23217739.
Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation. McCurry CL, Shepherd JD, Tropea D, Wang KH, Bear MF, Sur M. Nat Neurosci. 2010 Apr;13(4):450-7. doi: 10.1038/nn.2508. Epub 2010 Mar 14. PMID: 20228806.
In vivo two-photon imaging reveals a role of arc in enhancing orientation specificity in visual cortex. Wang KH, Majewska A, Schummers J, Farley B, Hu C, Sur M, Tonegawa S. Cell. 2006 Jul 28;126(2):389-402. PMID: 16873068.
Biochemical purification of a mammalian slit protein as a positive regulator of sensory axon elongation and branching. Wang KH, Brose K, Arnott D, Kidd T, Goodman CS, Henzel W, Tessier-Lavigne M. Cell. 1999 Mar 19;96(6):771-84. PMID: 10102266.
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